The present disclosure, in various embodiments, is directed to a photolytic apparatus that utilizes light energy to achieve physiological gas exchange in whole blood, such as in the blood stream of a patient experiencing respiratory difficulties, whole blood utilized to transport organs, etc., and to a photolytic cell or module used for the same. The disclosure finds particular applications in conjunction with the field of artificial organs and the medical arts. However, it is to be appreciated, that the embodiment disclosed herein will also find applications in related fields due to the photo-electro chemical transformations involved therein.
In this regard, despite major reduction in disease mortality experienced over the past several decades, the mortality associated with chronic lung disease has continued to rise. This is largely due to a lack of emerging treatments, and inadequate technology for providing intermediate (“bridge” therapy) or long-term respiratory support. Numerous technical solutions have been proposed and implemented. Moreno-Cabral R J, Dembitsky W P, Adamson R M, Daily P O., Percutaneous extracorporeal membrane oxygenation. Adv Card Surg, 5: 163-179, 1994; Funakubo A, Higami T, Sakuma I, Fukui Y, Kawamura T, Sato K, Sueoka A, Nose Y., Development of a membrane oxygenator for EXMO using a novel fine silicone hollow fiber, ASAIO, 42: M837-840, 1996; Naganuma S, Nitta S, Yambe T, Kobayashi S, Tanaka M, Hashimoto H., Gas exchange efficiency of a membrane oxygenator with use of a vibrating flow pump, Artif Organs, 19: 747-749, 1995; Yamane S, Ohashi Y, Sueoka A, Sato K, Kuwana J, Nose Y., Development of a silicone hollow fiber membrane oxygenator for ECMO application, ASAIO, 44: M384-387, 1998; Stammers A H, Fristoe L W, Alonso A, Song Z, Galbraith T., Clinical evaluation of a new generation membrane oxygenator: a prospective randomized study, Perfusion, 13: 165-175, 1998; Kitano Y, Takata M, Miyasaka K, Sasaki N, Zhang Q, Liu D, Tsuchida Y., Evaluation of an extracorporeal membrane oxygenation system using a nonporous membrane oxygenator and a new method for heparin coating, J Pediatric Surgery, 32: 691-697, 1997; Sueda T, Fukunmaga S, Morita S, Sueshiro M, Hirai S, Okada K, Orihashi K, Matsuura Y., Development of an intravascular pumping oxygenator using a new silicone membrane, Artif Organs, 21: 75-78, 1997; Mortensen J D, Berry G., Conceptual and design features of a practical, clinically effective intravenous mechanical blood oxygen/carbon dioxide exchange device (IVOX), Int J Artif Organs, 12: 384-389, 1989; and, Babley B, Bagley A, Henrie J, Fooerer C, Brohamer, J, Burkart J, Mortensen J D., Quantitative gas transfer into and out of circulating venous blood by means of an intra-vena caval Oxygenator, ASAIO Trans, 37: M413-415, 1991. However, none are believed, to this point, to provide sufficient yield, safety, and ease of use to support broad clinical deployment.
Furthermore, numerous improvements in lung transplantation have occurred due to advances in procurement, preservation, and implantation. Stammers A H, Fristoe L W, Alonso A, Song Z, Galbraith T., Clinical evaluation of a new generation membrane oxygenator: a prospective randomized study, Perfusion, 13: 165-175, 1998; Kitano Y, Takata M, Miyasaka K, Sasaki N, Zhang Q, Liu D, Tsuchida Y., Evaluation of an extracorporeal membrane oxygenation system using a nonporous membrane oxygenator and a new method for heparin coating, J Pediatric Surgery, 32: 691-697, 1997; Sueda T, Fukunmaga S, Morita S, Sueshiro M, Hirai S, Okada K, Orihashi K, Matsuura Y., Development of an intravascular pumping oxygenator using a new silicone membrane, Artif Organs, 21: 75-78, 1997; and, Mortensen J D, Berry G., Conceptual and design features of a practical, clinically effective intravenous mechanical blood oxygen/carbon dioxide exchange device (IVOX), Int J Artif Organs, 12: 384-389, 1989. However, the large discrepancy between the numbers of donors and recipients, the low yield of usable lungs, and the absence of temporizing methods for patients awaiting transplantation, make this option outside the reach of many patients.
Prior artificial lung technologies have been based on the delivery to the bloodstream of oxygen gas via hollow fibers, followed by back-and-forth diffusion across permeable membranes. Golob J F, Federspiel W J, Merrill T L, Frankowski B J, Kitwak K, Russian H, Hattler B G., Acute in vivo testing of an intravascular respiratory support catheter, ASAIO J, 47: 434-437, 2001; Federspiel W J, Hewitt T J, Hattler B G., Experimental evaluation of a model for oxygen exchange in a pulsating intravascular artificial lung, Ann Biomed Eng, 28: 160-167, 2000; and, Swischenberger J B, Anderson C M, Cook K E, Lick S D, Mockros L H, Bartlett R H., Development of an implantable artificial lung: challenges and progress, ASAIO J. 47: 316-20, 2001. These systems are attractive since gas exchange, analogous to that of the normal lung, is reliant on diffusivity and differential gas pressure on opposite sides of the membrane to drive O2/CO2 exchange. The principal weakness, however, of these systems is that they require the presence of major diffusion boundary layers, which results in slowed mass transport and the need for a large surface area to achieve sufficient flux of gases. In addition, these systems require a continuous source of exogenous pressurized O2 gas, generally via a tank or system of tanks.
The present disclosure seeks to circumvent one or more of the limitations set forth above by considering the problem of intravascular oxygenation from a fundamentally different perspective. Rather than delivering oxygen gas to the blood (or removing carbon dioxide against a back pressure of O2), the present disclosure uses photolytic energy to generate dissolved oxygen directly from the water already present in the blood, thereby eliminating the need for exogenous gas delivery, gas or liquid selective diffusion boundary layers, and the requirement for operating at or near equilibrium (FIG. 1). This approach thus constitutes a direct mechanism by which photolytically driven oxygenation of whole blood can occur.
It has previously been shown by Applicants that it is possible to generate dissolved oxygen directly from the water content of synthetic serum, based on the interaction of UV light with a semi-conducting titanium dioxide thin film. Dasse K A, Monzyk B F, Burckle E C, Busch J R, Gilbert R J., Development of a photolytic artificial lung, Preliminary concept validation, ASAIO Journal, 48:556-563, 2003. The opto-electronic interaction of a metal chelate chromophores with transition metal oxides is believed to be the basis for the well known phenomenon in nature, the light-dependent oxygen generation occurring in photosynthetic (PS) organisms, cyanobacteria, and, higher plants and algae. Limburg J, Vrettos J S, Liable-Sands L M, Rheingold A L, Crabtree R H, Bredvig G W., A functional model of O—O bond formation by the O2-evolving complex in photosystem II, Science, 283: 1524-1527, 1999; Vrettos J S, Brudvig G W., Water oxidation chemistry of photosystem II, Philos Trans Royal Society of London B Biol Sci, 357: 1395-1404, 2002; Yachandra V K, DeRose V J, Latimer M J, Mukerji I, Sauer K, Klein M P., Where plants make oxygen: a structural model for the photosynthetic oxygen-evolving manganese cluster, Science, 260: 675-679, 1993; and, Yachandra V K, Sauer K, Klein M P., Manganese cluster in photosynthesis: Where plants oxidize water to dioxygen, Chem Rev, 96: 2927-2950, 1996. The proposed photolytic lung technology disclosed herein thus builds upon the known ability of the metal oxide, the anatase form of titanium dioxide, TiO2, to serve both as the chromophore and the charge separation center. Fernandez-Ibanez P, Blanco J, Malato S, de las Nieves F J., Application of the colloidal stability of TiO2 particles for recovery and reuse in solar photocatalysis, Water Res. 37(13):3180-8, 2003; Topoglidis E, Campbell C J, Palomares E, Durrant J R., Photoelectrochemical study of Zn cytochrome-c immobilized on a nanoporous metal oxide electrode, Chem Commun (Camb). 21; (14): 1518-9, 2002; Hagfeldt A, Gratzel M., Molecular photovoltaics, Acc Chem. Res. 33(5):269-77, 2000; and, Tsai P, We C T, Lee C S., Electrokinetic studies of inorganic coated capillaries, J Chromatography B Biomed Appl. 657(2):285-90, 1994. The present disclosure describes and provides for the generation of dissolved oxygen, and the resulting increase of oxyhemoglobin, via photolytic means, in whole mammalian blood.